1,721,047 research outputs found
Metabolism and Functions of Platelet-Activating Factor (PAF) in the Nervous Tissue
No full textPlatelet Activating Factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was first identi- fied as a lipid mediator of inflammation and immunological response. This compound is present at very low concentration in normal mammalian brain where it is synthesized by two distinct pathways. The de novo pathway utilizes 1-alkyl-2-acetyl-sn-glycerol and CDP-choline as substrates of a DTT-insensitive phosphocholine transferase (PAF-PCT). The remodeling pathway requires the production of 1-alkyl-2- lyso-sn-glycero-3-phosphocholine (lysoPAF) produced by the hydrolysis of 1-alkyl-2-(long-chain)acyl- sn-glycero-3-phosphocholine (alkylacylGPC) by the action of phospholipases A2. Alternatively, lysoPAF can be produced by transacylation from alkylacyl-GPC to 1-alk-1’-enyl-2-lyso-sn-glycero-phosphoethano- lamine (lysoPlsEtn) produced by a phospholipase A2 as well. LysoPAF is acetylated to PAF by lysoPAF acetyltransferase (lysoPAF-AcT). The relative contribution of the two pathways to PAF synthesis depends on several factors including the concentration of substrates, energy availability, Ca2+ concentration, and phosphorylation state of key enzymes. PAF is transformed into the inactive lysoPAF by PAF acetylhydrolases (PAF-AH). Three intracellular isoforms of PAF-AH have been identified in mammalian brain. In neural cells, PAF is not stored and can be released into the extracellular space. Neural cells possess plasma membrane and intracellular receptors. Plasma membrane receptor (PAFR) has been pharmacologically characterized and cloned. This receptor is expressed in almost all brain areas. Cellular responses to the activation of PAFR are mediated by G-proteins and lead to a complex intracellular signaling. A number of natural and synthetic antagonists of PAFR and intracellular binding sites have been identified. In the brain, PAF participates im physiological mechanisms such as synaptic transmission, long-term potentiation, memory formation, proliferation and differentiation of neural cells, regulation of gene expression, and chemotaxis. Increased levels of PAF, due to upregulation of biosynthetic pathways or to downregulation of PAF-AH, have been observed in pathological conditions such as neuroinflammation, brain ischemia, and neurodegenerative diseases. Relatively high concentration of PAF causes neuronal death by apoptosis, which is linked to the neurotoxic effects of the execessive glutamate release, causing overloading of post-synaptic Ca2+ and the consequent activation of Ca2+-dependent enzymes including PLA2s
A thermal and thermo-chronological approach to study the evolution of the Eastern Sicily fold-and-thrust belt (Italy)
No full text
Attività antiossidante ed antinfiammatoria dei metaboliti bioattivi del latte di bufala
No full textThe quartzo-feldspathic granulites from External Liguride units (northern Apennine): geological setting, petrological features and age constraints
No full textThe geological and petrological features of the quartzo-feldspathic granulites recognized as slide blocks in the Mt. Ragola Complex (Santonian-Campanian) from External Liguride units, Northern Apennines, are described. Fission track analyses on zircons show that these rocks were exhumed in Late Palaeozoic times. A further thermal event in the Late Cretaceous has also been detected
Thermal and thermo-chronological evolution of the eastern Sicily fold-and-thrust belt (Italy): constraints from organic and inorganic parameters and fission track data
No full textReproducibility of apatite fission-track length data and thermal history reconstruction
No full textThe ability to derive detailed thermal history information from apatite fission-track analysis is predicated on the reliability of track length measurements. However, insufficient attention has been given to whether and how these measurements should be standardized. In conjunction with a fission-track workshop we conducted an experiment in which 11 volunteers measured ~50 track lengths on one or two samples. One mount contained Durango apatite with unannealed induced tracks, and one contained apatite from a crystalline rock containing spontaneous tracks with a broad length distribution caused by partial resetting. Results for both mounts showed scatter indicative of differences in measurement technique among the individual analysts. The effects of this variability on thermal history inversion were tested using the HeFTy computer program to model the spontaneous track measurements. A cooling-only scenario and a reheating scenario more consistent with the sample's geological history were posed. When a uniform initial length value from the literature was used, results among analysts were very inconsistent in both scenarios, although normalizing for track angle by projecting all lengths to a c-axis parallel crystallographic orientation improved some aspects of congruency. When the induced track measurement was used as the basis for thermal history inversion congruency among analysts, and agreement with inversions based on data previously collected, was significantly improved. Further improvement was obtained by using c-axis projection. Differences among inversions that persisted could be traced to differential sampling of long- and short-track populations among analysts. The results of this study, while demonstrating the robustness of apatite fission-track thermal history inversion, nevertheless point to the necessity for a standardized length calibration schema that accounts for analyst variation
Ergothioneine oxidation protects against high-glucose induced endothelial senescence via SIRT1 and SIRT6
No full textThermal and thermo-chronological constraints to burial-exhumation history of Eastern Sicily fold-and-thrust belt
No full textSIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection.
No full textSIGNIFICANCE:
Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD+)-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged.
CRITICAL ISSUES:
We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level.
FUTURE DIRECTIONS:
A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple "omic" technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732
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